Avastin May Do More Harm than Good

There's more bad news about the cancer drug Avastin. A review of previous studies suggests that treatment with Avastin causes more deaths than treatment with chemotherapy or biologic agents alone. The review found that patients taking Avastin in combination with a chemotherapy or biologic agent were nearly 50% more likely to die from the treatment than patients taking the chemotherapy or biologic agent alone.

In patients receiving taxanes or platinum agents, the risk of death was 3.5 times as high when they also took Avastin. In patients receiving other chemotherapy agents, Avastin did not increase the rate of treatment-related death.

The review did not look at overall death or survival rates. It only looked at deaths that were most likely caused by the cancer treatment itself. These are known as fatal adverse events or FAEs.

Avastin (bevacizumab) is an antibody against a factor that causes growth of new blood vessels. It can kill cancer cells by interfering with their blood supply. It can also cause problems with the blood metabolism of normal tissues, leading to increased risk of hemorrhaging or drastic lowering of white blood cell count (neutropenia), the two most frequent causes of death found in the review.

Controversy has surrounded Avastin since its initial approval. In February 2008, the drug was approved by the FDA for treatment of metastatic breast cancer despite an advisory panel voting 5-4 against approval the previous December. A single clinical trial had showed Avastin to slow tumor growth but showed no improvement in overall patient survival. The FDA approval was contingent on further studies showing benefits of Avastin treatment.

Since its approval, Avastin has been used to treat many different types of cancers.

Three subsequent studies of Avastin failed to find a survival benefit from its use. In December 2010, the FDA recommended removing the breast cancer indication from Avastin's label, essentially overturning its initial approval, though the drug was not removed from the market. This recommendation did not apply to Avastin use for colon, brain, lung and kidney cancer.

The recent review looked at 16 trials of Avastin involving over 10,000 patients with various types of advanced cancer. The trials all compared patients taking Avastin plus a chemotherapy or biologic agent to patients taking the chemotherapy or biologic agent alone. It found that 2.5% of patients taking Avastin had died from a treatment-related cause, compared with 1.7% of the patients who did not take Avastin. This is a 46% increased risk of death.

The treatment-related death rate did not vary with cancer type but did vary with the type of chemotherapy agent patients were receiving. In patients receiving taxanes or platinum agents, the risk was 3.5 times as high when they also took Avastin. In patients receiving other chemotherapy agents, Avastin did not increase the rate of treatment-related death.

Because this review only looks at deaths stemming from cancer treatment, it does not add any information to the ongoing debate over whether treatment with Avastin lowers the death rate from cancer or increases the overall survival rate of cancer patients.

An editorial accompanying the review suggests that Avastin works well in some patients but that it is currently not possible to tell which patients will benefit from Avastin and which will not.

Avastin treatment costs $50,000 per year for the drug alone and is difficult to administer, requiring frequent injections. Add in the uncertainty about its effectiveness and doctors and patients alike may have a difficult time deciding who might be a good candidate for Avastin treatment.

Both the review and the editorial appear in the Feb 2, 2011 issue of the Journal of the American Medical Association (JAMA).